Versatile and on-demand biologics co-production in yeast

Current limitations to on-demand drug manufacturing can be addressed by technologies that streamline manufacturing processes. Combining the production of two or more drugs into a single batch could not only be useful for research, clinical studies, and urgent therapies but also effective when combin...

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Main Authors: Cao, Jicong, Perez-Pinera, Pablo, Lowenhaupt, Ky, Wu, Ming-Ru, Purcell, Oliver, de la Fuente-Nunez, Cesar, Lu, Timothy K., de la Fuente Nunez, Cesar, Lu, Timothy K
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Published: Nature Publishing Group 2018
Online Access:http://hdl.handle.net/1721.1/115215
https://orcid.org/0000-0002-5253-3365
https://orcid.org/0000-0002-8187-6498
https://orcid.org/0000-0002-2533-8484
https://orcid.org/0000-0002-2031-8871
https://orcid.org/0000-0002-9999-6690
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author Cao, Jicong
Perez-Pinera, Pablo
Lowenhaupt, Ky
Wu, Ming-Ru
Purcell, Oliver
de la Fuente-Nunez, Cesar
Lu, Timothy K.
de la Fuente Nunez, Cesar
Lu, Timothy K
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Cao, Jicong
Perez-Pinera, Pablo
Lowenhaupt, Ky
Wu, Ming-Ru
Purcell, Oliver
de la Fuente-Nunez, Cesar
Lu, Timothy K.
de la Fuente Nunez, Cesar
Lu, Timothy K
author_sort Cao, Jicong
collection MIT
description Current limitations to on-demand drug manufacturing can be addressed by technologies that streamline manufacturing processes. Combining the production of two or more drugs into a single batch could not only be useful for research, clinical studies, and urgent therapies but also effective when combination therapies are needed or where resources are scarce. Here we propose strategies to concurrently produce multiple biologics from yeast in single batches by multiplexing strain development, cell culture, separation, and purification. We demonstrate proof-of-concept for three biologics co-production strategies: (i) inducible expression of multiple biologics and control over the ratio between biologic drugs produced together; (ii) consolidated bioprocessing; and (iii) co-expression and co-purification of a mixture of two monoclonal antibodies. We then use these basic strategies to produce drug mixtures as well as to separate drugs. These strategies offer a diverse array of options for on-demand, flexible, low-cost, and decentralized biomanufacturing applications without the need for specialized equipment.
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spelling mit-1721.1/1152152022-10-02T04:36:35Z Versatile and on-demand biologics co-production in yeast Cao, Jicong Perez-Pinera, Pablo Lowenhaupt, Ky Wu, Ming-Ru Purcell, Oliver de la Fuente-Nunez, Cesar Lu, Timothy K. de la Fuente Nunez, Cesar Lu, Timothy K Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology. Research Laboratory of Electronics Cao, Jicong Perez-Pinera, Pablo Lowenhaupt, Ky Wu, Ming-Ru Purcell, Oliver de la Fuente Nunez, Cesar Lu, Timothy K Current limitations to on-demand drug manufacturing can be addressed by technologies that streamline manufacturing processes. Combining the production of two or more drugs into a single batch could not only be useful for research, clinical studies, and urgent therapies but also effective when combination therapies are needed or where resources are scarce. Here we propose strategies to concurrently produce multiple biologics from yeast in single batches by multiplexing strain development, cell culture, separation, and purification. We demonstrate proof-of-concept for three biologics co-production strategies: (i) inducible expression of multiple biologics and control over the ratio between biologic drugs produced together; (ii) consolidated bioprocessing; and (iii) co-expression and co-purification of a mixture of two monoclonal antibodies. We then use these basic strategies to produce drug mixtures as well as to separate drugs. These strategies offer a diverse array of options for on-demand, flexible, low-cost, and decentralized biomanufacturing applications without the need for specialized equipment. 2018-05-03T17:44:07Z 2018-05-03T17:44:07Z 2018-01 2017-03 2018-04-27T16:17:34Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/115215 Cao, Jicong et al. “Versatile and on-Demand Biologics Co-Production in Yeast.” Nature Communications 9, 1 (January 2018): 77 © 2017 The Author(s) https://orcid.org/0000-0002-5253-3365 https://orcid.org/0000-0002-8187-6498 https://orcid.org/0000-0002-2533-8484 https://orcid.org/0000-0002-2031-8871 https://orcid.org/0000-0002-9999-6690 http://dx.doi.org/10.1038/s41467-017-02587-w Nature Communications Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature Communications
spellingShingle Cao, Jicong
Perez-Pinera, Pablo
Lowenhaupt, Ky
Wu, Ming-Ru
Purcell, Oliver
de la Fuente-Nunez, Cesar
Lu, Timothy K.
de la Fuente Nunez, Cesar
Lu, Timothy K
Versatile and on-demand biologics co-production in yeast
title Versatile and on-demand biologics co-production in yeast
title_full Versatile and on-demand biologics co-production in yeast
title_fullStr Versatile and on-demand biologics co-production in yeast
title_full_unstemmed Versatile and on-demand biologics co-production in yeast
title_short Versatile and on-demand biologics co-production in yeast
title_sort versatile and on demand biologics co production in yeast
url http://hdl.handle.net/1721.1/115215
https://orcid.org/0000-0002-5253-3365
https://orcid.org/0000-0002-8187-6498
https://orcid.org/0000-0002-2533-8484
https://orcid.org/0000-0002-2031-8871
https://orcid.org/0000-0002-9999-6690
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